1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 59490916, compound

HRID 1952225Notes

Reaction equation

HRID 1952225 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([CH3:14])=[CH:11][CH:12]=2)[C:7]([C:15]2[C:16]([O:21][CH3:22])=[N:17][CH:18]=[CH:19][CH:20]=2)=[C:6]1[C:23]([OH:25])=O.C(C1NC=CN=1)(C1NC=CN=1)=O.[CH:42]1([S:45]([NH2:48])(=[O:47])=[O:46])[CH2:44][CH2:43]1.N12CCCN=C1CCCCC2>O1CCCC1.C(OCC)(=O)C.O>[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[N:9][C:10]([CH3:14])=[CH:11][CH:12]=2)[C:7]([C:15]2[C:16]([O:21][CH3:22])=[N:17][CH:18]=[CH:19][CH:20]=2)=[C:6]1[C:23]([NH:48][S:45]([CH:42]1[CH2:44][CH2:43]1)(=[O:47])=[O:46])=[O:25]

Participants

8

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 15765418CyclopropanesulfonamideHCID 59490928HCID 59490928, compound

Product 1

HCID 59490916HCID 59490916, compoundYield 72.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(2-Fluoro-benzyl)-3-(2-methoxy-pyridin-3-yl)-5-methyl-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid B5 (100 mg, 0.25 mmol) was diluted with tetrahydrofuran (3 mL) and to the resulting solution was added carbonyl diimidazole (62 mg, 0.38 mmol). The resulting suspension was heated to reflux and allowed to stir at this temperature for 1 hour. The reaction mixture was cooled to room temperature and cyclopropanesulfonamide (46 mg, 0.38 mmol) and 1,8-diazabicyclo(5.4.0)undec-7-ene (76 mg, 0.5 mmol) was added. The resulting reaction was stirred at room temperature for an additional 14 hours, then concentrated in vacuo. The residue obtained was diluted with ethyl acetate (100 mL) and water (10 mL). The organic layer was separated and the aqueous layer extracted twice more with ethyl acetate (2×20 mL). The combined organic layers were dried (magnesium sulfate), filtered and concentrated in vacuo to provide a crude residue which was purified using flash chromatography to provide cyclopropanesulfonic acid [1-(2-fluoro-benzyl)-3-(2-methoxy-pyridin-3-yl)-5-methyl-1H-pyrrolo[3,2-b]pyridine-2-carbonyl]-amide B6 (0.09 g, 72% yield). MS: 495.3 (M+H)+.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux
  3. customThe resulting reaction
  4. stirringwas stirred at room temperature for an additional 14 hours
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customThe organic layer was separated
  8. extractionthe aqueous layer extracted twice more with ethyl acetate (2×20 mL)
  9. dry with materialThe combined organic layers were dried (magnesium sulfate)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a crude residue which
  13. customwas purified

Sources & evidence

ORD record
ord-7d2572f8045546b7a3f444d6feaca207
Source dataset
uspto-grants-2013_03
Patent number
US08404845B2

Reaction notes

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